Διαγνωστικά προβλήματα στη θρομβοεμβολική νόσο (στη πνευμονική εμβολή)

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1 Διαγνωστικά προβλήματα στη θρομβοεμβολική νόσο (στη πνευμονική εμβολή) Ελευθέριος Ζέρβας, Πνευμονολόγος Επιμελητής Α ΕΣΥ 7 η Πνευμονολογική Κλινική Γ.Ν.Ν.Θ.Α «Η ΣΩΤΗΡΙΑ» 8-10 Δεκεμβρίου 2016 Ξενοδοχείο Royal Olympic, ΑΘΗΝΑ

2 Conflict of interest (Δήλωση σύγκρουσης συμφερόντων) Συμμετοχή σε advisory board (συμβουλευτική επιτροπή) των φαρμακευτικών εταιρειών Astra, Elpen, GSK, Menarini, MSD, Novartis Honorarium (τιμητικές αμοιβές) ως προσκεκλημένος ομιλητής από τις φαρμακευτικές εταιρείες Astra, Boehringer, Elpen, GSK, Menarini, Novartis, USB Κάλυψη εξόδων συμμετοχής (εγγραφής, ταξιδίου και διαμονής) σε ελληνικά και διεθνή συνέδρια από τις φαρμακευτικές εταιρείες Astra, Boehringer, Chiezi, Galenica, GSK, Elpen, MSD, Novartis, Roche

3 Διαγνωστικά προβλήματα στη θρομβοεμβολική νόσο (ΠΕ) Γενικά στοιχεία για τη θρομβοεμβολική νόσο Υπάρχουν ειδικά συμπτώματα και κλινικά ευρήματα? Ποια βοήθεια προσφέρει ο αρχικός εργαστηριακός/απεικονιστικός έλεγχος? O ρόλος των αλγορίθμων κλινικής πιθανότητας ΠΕ O ρόλος του D-dimer στο διαγνωστικό αλγόριθμο Διάγνωση ΠΕ με την CTPA, σπινθηρογράφημα αιμάτωσης, U/S καρδίας Ειδικά θέματα προβληματισμού Συμπεράσματα

5 Γενικά στοιχεία για τη θρομβοεμβολική νόσο (ΠΕ) Venous thromboembolism (VTE) encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE). It is the third most frequent cardiovascular disease with an overall annual incidence of per inhabitants. Acute PE is the most serious clinical presentation of VTE Konstantinides S. et al. ESC Guidelines European Heart Journal 2014

6 Γενικά στοιχεία για τη θρομβοεμβολική νόσο (ΠΕ) Since patients older than 40 years are at increased risk compared with younger patients and the risk approximately doubles with each subsequent decade, an ever-larger number of patients are expected to be diagnosed with (and perhaps die of) PE in the future Konstantinides S. et al. ESC Guidelines European Heart Journal 2014

7 Γενικά στοιχεία για τη θρομβοεμβολική νόσο (ΠΕ) Overall, PE is a major cause of mortality, morbidity, and hospitalization in Europe. As estimated on the basis of an epidemiological model, over deaths were related to VTE in six countries of the European Union (with a population of million) in 2004 Of these cases, 34% presented with sudden fatal PE and 59% were deaths resulting from PE that remained undiagnosed during life only 7% of the patients who died early were correctly diagnosed with PE before death (Cohen AT et al. 2007). Konstantinides S. et al. ESC Guidelines European Heart Journal 2014

8 Γενικά στοιχεία για τη θρομβοεμβολική νόσο (ΠΕ) 2 clinical scenarios (the asymptomatic patient and the patient presenting in cardiac arrest) define the extremities of the clinical spectrum of PE, with every possible presentation in between PE is often found on CT scans performed on suspicion of completely different conditions, for example when staging extrapulmonary cancers. A recent meta-analysis of 35,990 cancer patients found that unsuspected PE was seen in 552 patients corresponding to a mean weighted prevalence of 1.8 % (Donadini et al. 2014). In other patients, PE presents dramatically as sudden cardiac arrest without any prodromes. Around one third of patients presenting with pulseless electrical activity cardiac arrest turns out to have unsuspected PE (Comess et al. 2000). Madsen PH et al Adv Exp Med Biol 2016

10 Υπάρχουν ειδικά συμπτώματα στη θρομβοεμβολική νόσο (ΠΕ)? Even though some patients are asymptomatic, the patient with PE generally presents with symptoms from the cardiopulmonary system. Although these symptoms are often due to serious disease, they are non-specific and thereby non-diagnostic.

11 Υπάρχουν ειδικά συμπτώματα στη θρομβοεμβολική νόσο (ΠΕ)? But.4 main symptoms of PE (acute onset dyspnea, chest pain, syncope, and hemoptysis) are almost always present, either alone or in combination, if the patient is not asymptomatic. Madsen PH et al Adv Exp Med Biol 2016

12 Υπάρχουν ειδικά κλινικά ευρήματα στη θρομβοεμβολική νόσο (ΠΕ)? Moreover, no clinical important differences in vital signs are found between patients with or without PE (Goldhaber et al. 2010, Miniati et al. 1999). Likewise, no physical findings are reported to either confirm or rule-out PE, although signs of deep vein thrombosis are found more frequently in patients with PE than patients without PE Madsen PH et al Adv Exp Med Biol 2016

14 Ποια βοήθεια προσφέρει ο αρχικός εργαστηριακός/απεικονιστικός έλεγχος? Arterial blood gas : Hypoxemia is present in most patients with PE, but is also present in many other conditions. The same is true for hypocapnia and abnormal (A a) DO2 gradient Up to 40% of the patients with PE have normal arterial oxygen saturation and 20% a normal alveolar-arterial oxygen gradient (Rodger et al. 2000, Stein PD et al. 1996). However, unsuspected hypocapnia in a patient with COPD exacerbation could be a clue that PE is present (Akpinar et al. 2014).

15 Ποια βοήθεια προσφέρει ο αρχικός εργαστηριακός/απεικονιστικός έλεγχος? Chest X-Ray: Most patients with PE present with some abnormalities on the chest x-ray. These are, however, almost always non-specific In general, the chest x-ray is important as an initial investigation in patients with clinical features of PE, as important differential diagnosis, like pneumothorax, can be diagnosed this way Elliott et al. 2000

16 Ποια βοήθεια προσφέρει ο αρχικός εργαστηριακός/απεικονιστικός έλεγχος? ECG: Multiple ECG changes in PE have been reported. The findings of ECG cannot by themselves either rule in or out PE. The ECG therefore serves primarily as an important tool in differential diagnostics. In milder cases, the only anomaly may be sinus tachycardia, present in 40% of patients. Madsen PH et al Adv Exp Med Biol 2016

18 O ρόλος των αλγορίθμων κλινικής πιθανότητας ΠΕ Multiple clinical prediction scores have been suggested, of which the Wells score (Wells et al. 2000) and revised Geneva score (Le Gal et al. 2006) are widely used. One of the most notable weaknesses of the Wells score is the subjective judgment of An alternative diagnosis less likely than PE. This has been criticized, as it leads to some degree of begging the question.

19 O ρόλος των αλγορίθμων κλινικής πιθανότητας ΠΕ Multiple clinical prediction scores have been suggested, of which the Wells score (Wells et al. 2000) and revised Geneva score (Le Gal et al. 2006) are widely used. The clinical scoring systems are used primarily to guide whether further work up for PE is appropriate, and in many circumstances they do indeed provide guidance. However

20 O ρόλος των αλγορίθμων κλινικής πιθανότητας ΠΕ However this is not always the case, and then a clinical judgment is crucial and has to incorporate other parameters than those in the Wells and revised Geneva scores Madsen PH et al Adv Exp Med Biol 2016

22 O ρόλος του D-dimer στο διαγνωστικό αλγόριθμο No role in suspected pulmonary embolism with shock or hypotension. a negative d-dimer should not rule out PE when the clinical probability is high Konstantinides S. et al. ESC Guidelines European Heart Journal 2014

23 O ρόλος του D-dimer στο διαγνωστικό αλγόριθμο The negative predictive value of D-dimer testing is high and a normal D-dimer level renders acute PE or DVT unlikely The positive predictive value of elevated D-dimer levels is low and D-dimer testing is not useful for confirmation of PE Konstantinides S. et al. ESC Guidelines European Heart Journal 2014

24 O ρόλος του D-dimer στο διαγνωστικό αλγόριθμο Ειδικά θέματα και προβλήματα με το D-dimer Different d-dimer assays are available, with different diagnostic performance. When using a high sensitivity-assay like the quantitative enzyme-linked immunosorbent assay (ELISA) or ELISA-derived assays, the sensitivity and negative predictive values are very high (Stein et al. 2004). Factors that, among others, can cause false-positive d-dimer are increasing age, cocaine use, immobility, hemoptysis, hemodialysis, malignancy, rheumatoid arthritis, systemic lupus erythematosus, sickle cell disease, severe infections, pregnancy, postpartum state and surgery (Kline and Kabrhel 2015) The specificity of D-dimer in suspected PE decreases steadily with age, to almost 10% in patients.80 years. Recent evidence suggests using age-adjusted cut-offs to improve the performance of D-dimer testing in the elderly (Righini M et al 2000, Penaloza A et al 2012)

26 Διάγνωση ΠΕ με την CTPA, σπινθηρογράφημα αιμάτωσης, U/S καρδίας Ειδικά θέματα και προβλήματα με την CTPA Computed tomographic (CT) angiography has become the method of choice for imaging the pulmonary vasculature in patients with suspected PE In patients with a low or intermediate clinical probability of PE as assessed by the Wells rule, a negative CT had a high negative predictive value for PE (96% and 89%, respectively), whereas this was only 60% in those with a high pre-test probability. Conversely, the positive predictive value of a positive CT was high (92 96%) in patients with an intermediate or high clinical probability but much lower (58%) in patients with a low pre-test likelihood of PE (Stein PD, et al N Engl J Med 2006) The clinical significance of isolated sub-segmental PE on CT angiography is questionable.. The incidental discovery of clinically unsuspected PE on CT is an increasingly frequent problem. Konstantinides S. et al. ESC Guidelines European Heart Journal 2014

27 Διάγνωση ΠΕ με την CTPA, σπινθηρογράφημα αιμάτωσης, U/S καρδίας Ειδικά θέματα και προβλήματα με το σπινθηρογράφημα αιμάτωσης Ventilation perfusion scintigraphy (V/Q scan) is an established diagnostic test for suspected PE Performing only a perfusion scan is acceptable in patients with a normal chest X-ray; any perfusion defect in this situation will be considered to be a mismatch To facilitate communication with clinicians, a threetier classification is preferable: normal scan (excluding PE), high probability scan (considered diagnostic of PE in most patients), and non-diagnostic scan Τhe high frequency of non-diagnostic intermediate probability scans has been a cause for criticism.. Konstantinides S. et al. ESC Guidelines European Heart Journal 2014

28 Διάγνωση ΠΕ με την CTPA, σπινθηρογράφημα αιμάτωσης, U/S καρδίας Ειδικά θέματα και προβλήματα με το U/S καρδίας Acute PE may lead to RV pressure overload and dysfunction, which can be detected by echocardiography Given the peculiar geometry of the RV, there is no individual echocardiographic parameter that provides fast and reliable information on RV size or function.. Konstantinides S. et al. ESC Guidelines European Heart Journal 2014

30 Ειδικά θέματα προβληματισμού Πνευμονική εμβολή και καρκίνος Jasmijn F. et al. Blood 2013 A negative D-dimer test has the same diagnostic value as in non-cancer patients. On the other hand, D-dimer levels are non-specifically increased in many patients with cancer The widespread use of CT scanners has resulted in an increasing number of incidentally diagnosed, asymptomatic PEs in cancer patients = TREAT as symptomatic PE Konstantinides S. et al. ESC Guidelines European Heart Journal 2014

31 Ειδικά θέματα προβληματισμού Πνευμονική εμβολή και καρκίνος Patients with acute unprovoked VTE have a four-fold increased risk of having an underlying occult cancer compared to patients with provoking (e.g. recent surgery) risk factors Up to 10 % of patients with unprovoked VTE may be diagnosed with cancer within the first year following their thrombotic event Khorana. et al. J Thromb Thrombolysis 2016

33 Συμπεράσματα Symptoms of PE (like dyspnea, chest pain, hemoptysis and syncope) are non-specific, but inevitably warrants further diagnostic work-up Basic work up in patients with symptoms of PE comprises, in part, of arterial blood gas analysis, ECG, chest x-ray and venous blood sampling and these investigations are primarily important in establishing differential diagnosis and in risk stratification Clinical prediction score systems like the Wells score and revised Geneva score can, along with d-dimer, be used to guide if diagnostic imaging like CT-angiography or V/Q-scan on suspicion of PE is warranted When the diagnosis of PE is established, risk stratification is warranted e.g. using the PESIscore and assessment of right heart function by echocardiography to guide location of treatment, monitoring, treatment and prognosis

34 Διαγνωστικά προβλήματα στη θρομβοεμβολική νόσο (ΠΕ)